AN ABNORMALITY OF THYROID-HORMONE RECEPTOR EXPRESSION MAY EXPLAIN ABNORMAL THYROTROPIN PRODUCTION IN THYROTROPIN-SECRETING PITUITARY-TUMORS

Thyrotropin (TSH)-secreting pituitary adenomas cause hyperthyroxinemia in the presence of ''inappropriately'' elevated concentrations of TSH . TSH production under these circumstances escapes the normal negative feedback effect of thyroid hormone. We propose that this defective ne gative feedback is mediated by an abnormality of thyroid hormone recep tor (TR) expression. Two TSH-secreting pituitary adenomas were analyze d by immunocytochemistry for TR isoform protein expression and by semi quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for TR isoform mRNA expression, The results obtained from these tumors were compared with the findings from six normal human pituitaries. Ne ither tumor examined expressed detectable levels of nuclear TR alpha o r TR beta proteins, in contrast to the normal pituitaries studied, whi ch expressed all TR isoforms. Application of RT-PCR, however, revealed mRNAs encoding each TR isoform in all tumorous and normal tissues exa mined. Semiquantitative RT-PCR revealed similar levels of expression o f TR alpha and TR beta isoform mRNAs in tumors and normal tissue, in c ontrast to the observed difference in TR proteins. Absent TR alpha and TR beta protein expression, in association with normal mRNA levels, i mplies a post-transcriptional defect in TR mRNA processing in TSH-secr eting adenomas. Reduced TR expression in these tumors may explain defe ctive negative feedback of thyroid hormone on TSH production, and may also contribute to uncontrolled tumor growth.